In order to reach their intestinal habitat, enteric microbes must first survive the formidable low pH environment of the stomach, making an acid-coping strategy imperative. Wild-type Salmonella enterica serotypes have multiple ways to resist low pH. First, the acid tolerance response (ATR) upregulates acid shock proteins to temporarily prevent cellular damage. Second, the acid resistance systems (AR) consume protons to raise the intracellular pH. AR1 system is regulated by Crp and is poorly understood. The remaining systems, AR3, AR4 and AR5 (AR2 is not present in Salmonella) rely on arginine, lysine and ornithine decarboxylases, respectively. However, AR3-5 are typically repressed under standard laboratory growth conditions, and the ATR in many live attenuated Salmonella vaccines is impaired, making gastric transit challenging for these strains. In addition, many means used to attenuate Salmonella for virulence have a secondary effect of increasing sensitivity to acid, thereby increasing the effective dose required for immunogenicity. As a result, oral Salmonella vaccines are typically given with an agent designed to increase the gastric pH, such as bicarbonate. While this approach is helpful, it precludes the Salmonella vaccine from sensing important environmental signals (i.e. low pH) that optimize its ability to effectively interact with host tissues. This results in reduced immunogenicity as a vaccine.